University of California, Irvine Ph.D. (1972) Psychobiology University of North Carolina, Chapel Hill, Postdoc, (1972-1974) Neurobiology

Mentor:

McGaugh, James , PhD.

Research Description:

Our group has a long-standing interest in the neurobiology of brain aging, Alzheimer’s disease and associated cognitive decline. To study these phenomena at fundamental levels, my lab has used a multidisciplinary approach that has included behavioral testing, single-cell electrophysiology, endocrinology, molecular biology, viral vector gene manipulation, immunohistochemistry, E.M., and extensive gene microarray analyses of animal and human brain tissues. Our recent work has focused on determining when the markers of unhealthy brain aging begin to emerge and identifying the underlying pathways that may play a mechanistic role. In addition, we are investigating the interactions among the multiple processes altered with brain aging/AD. We have also conducted numerous long-term studies using steroid hormonal/pharmacological intervention treatments, attempting to retard the course of brain decline and test basic mechanistic hypotheses. These approaches have revealed that the onset of unhealthy brain aging is associated with the emergence of hippocampal neuronal Ca2+ dysregulation and reactive glial processes related to glucocorticoid signaling, lipid/glucose metabolism, inflammation and myelin programs, among other processes. Our experience with brain aging, multidisciplinary approaches and statistical analyses of massive gene array datasets appears to place us in a favorable position for elucidating mechanisms and potential targets of cognitive decline in Alzheimer’s disease and brain aging.

Chen, KC ; Blalock, EM ; Thibault, O.; Kaminker, P.; Landfield, PW "Expression of alpha 1D subunit mRNA is correlated with L-type Ca2+ channel activity in single neurons of hippocampal "zipper" slices."Proceedings of the National Academy of Sciences of the United States of America97,8(2000):4357-62.[PubMed Link] | [ Full text ]

Blalock, EM ; Porter, NM ; Landfield, PW "Decreased G-protein-mediated regulation and shift in calcium channel types with age in hippocampal cultures."The Journal of neuroscience : the official journal of the Society for Neuroscience19,19(1999):8674-84.[PubMed Link] | [ Full text ]

Landfield, PW "Increased hippocampal Ca2+ channel activity in brain aging and dementia. Hormonal and pharmacologic modulation."Annals of the New York Academy of Sciences747,(1994):351-64.[PubMed Link] | [ Full text ]

Thibault, O.; Porter, NM ; Landfield, PW "Low Ba2+ and Ca2+ induce a sustained high probability of repolarization openings of L-type Ca2+ channels in hippocampal neurons: physiological implications."Proceedings of the National Academy of Sciences of the United States of America90,24(1993):11792-6.[PubMed Link] | [ Full text ]

Applegate, MD ; Landfield, PW "Synaptic vesicle redistribution during hippocampal frequency potentiation and depression in young and aged rats."The Journal of neuroscience : the official journal of the Society for Neuroscience8,4(1988):1096-111.[PubMed Link] | [ Full text ]